The idiotype network developed during the course of an immune response provides conceptual insight into the host response to a given antigen. It is proposed to analyze the idiotype networks initiated by a host in response to a hepatitis B virus (HBV) infection or immunization with hepatitis B surface antigen (HBsAg). Monoclonal anti-idiotypic antibody (anti-Id) reagents will be generated against polyclonal and monoclonal human antibodies to HBsAg (anti-HBs). These anti-Id will be serologically characterized in order to assess whether they are representative of the Ab-2 beta internal, image class or Ab-2 alpha subclasses of anti-Id. The ability of these different classes of anti-Id to modulate the humoral and cell mediated immune response to HBsAg in experimental animals will be examined. The anti-Id induced anti- HBs (Ab-3) responses will be analyzed for idiotype expression. Anti-HBs fine specificity of this anti-Id induced response will also be assessed using HBsAg synthetic peptides. We will also assess the cell mediated immune response induced by anti-Id immunization. Possible genetic restriction reported in other systems with the Ab-2 alpha classes of anti-Id will be examined in the anti-HBs system using different inbred strains of mice for anti-Id immunization. The potential effects the different classes of monoclonal anti-Id may have on the serological characteristics of an anti-HBs Ab-3 response and cell-mediated immune response will be determined and compared relative to immunization with the nominal antigen (HBsAg). Conversely, we will examine the idiotype heterogeneity of the human and chimpanzee immune response to HBsAg utilizing those monoclonal anti-Id which detect shared anti-HBs idiotypes present in HBV infected and HBsAg vaccinated individuals. We will further characterize the immune response in anti-Id vaccinated chimpanzees. Finally, we will determine if an auto- anti-Id response can be detected in mice immunized with HBsAg or synthetic peptides and in chimpanzees and humans infected with HBV. Monoclonal auto-anti-Id will be generated and compared with monoclonal anti-Id induced by human anti-HBs Ab-1 immunization. The results of these experiments will give further insight on the ability of different classes of anti-Id to modulate the immune response to a viral antigen, namely HBsAg. In addition, these studies should provide information into whether idiotype networks, expression of particular idiotypes or both are important in the host response to HBV.